The Correlation between Plasma IL-17 Levels, Lymphocyte Counts, and Neutrophil Counts with the Colonisation of Candida sp. in Tuberculosis Patients with a Treatment History
DOI:
https://doi.org/10.20956/nmsj.v10i2.46139Abstract
Introduction: Tuberculosis (TB) patients with a history of ATT therapy are associated with changes in IL-17 levels, lymphocyte counts, and neutrophil counts. Increased IL-17 levels, lymphocyte counts and neutrophil counts indicate colonisation of Candida sp. fungus. Changes in the immune response in TB patients with Candida sp. colonisation may cause complications of TB that affect the treatment success rate. Methods: This research was designed for observational analytical study with a cross-sectional design. 59 subjects are divided into 3 groups, consisting of 21 TB-positive people with Candida sp. colonisation, 21 TB-positive people without Candida sp. colonisation, and 17 TB-negative people with Candida sp. colonisation. Plasma IL-17 levels are examined using the ELISA test, while the lymphocyte and neutrophil counts are seen from previous study examinations (AFFECT). Results: The plasma IL-17 levels in the TB-positive group with Candida sp. colonisation were 24.05 pg/ml (IQR 21.77-30.50). The plasma IL-17 levels in the TB-positive group without Candida sp colonisation were 23.08 pg/ml (IQR 19.11-32.46). The plasma IL-17 levels in the TB-negative group with Candida sp. colonisation is 20.72 pg/ml (IQR 18.51-22.84) pg/ml, (p=0.046). However, there are no statistically significant difference was observed in lymphocyte and neutrophil counts (p=0.078). Conclusions: The differences in IL-17 levels that occur in the TB group with Candida sp colonisation may serve as an immunological signal suggesting the need for fungal assessment if the TB patients do not improve their treatment outcome after undergoing ATT for over 6 months.
References
1. Kementerian Kesehatan RI. https://yankes.kemkes.go.id/. 2022. p. 1–3 Kepatuhan Pengobatan pada Tuberculosis.
2. Kementerian Kesehatan RI. Pedoman Nasional Tata Laksana Tuberkulosis. Kemenkes RI. 2020;1–156.
3. Vila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA. Oral candidiasis: A disease of opportunity. Journal of Fungi. 2020 Mar 1;6(1):1–28.
4. Talapko J, Juzbašić M, Matijević T, Pustijanac E, Bekić S, Kotris I, et al. Candida albicans-the virulence factors and clinical manifestations of infection. Journal of Fungi. 2021 Feb 1;7(2):1–19.
5. World Health Organization. WHO fungal priority pathogens list to guide research, development and public health action. 2022.
6. Soedarsono S, Prasetiyo Y, Mertaniasih N. Fungal isolates findings of sputum samples in new and previously treated cases of pulmonary tuberculosis in dr. soetomo hospital surabaya, Indonesia. International Journal of Mycobacteriology. 2020 Apr 1;9(2):190–4.
7. Astekar M, Bhatiya PS, Sowmya G V. Prevalence and characterization of opportunistic candidal infections among patients with pulmonary tuberculosis. Journal of Oral Maxillofacial Pathology. 2016 May 1;20(2):183–9.
8. Abay F, Yalew A, Shibabaw A, Enawgaw B. Hematological Abnormalities of Pulmonary Tuberculosis Patients with and without HIV at the University of Gondar Hospital, Northwest Ethiopia: A Comparative Cross-Sectional Study. Tuberculosis Research and Treatment. 2018 Dec 30;20(18):1–6.
9. Xu L, Cui G, Jia H, Zhu Y, Ding Y, Chen J, et al. Decreased IL-17 during treatment of sputum smear-positive pulmonary tuberculosis due to increased regulatory T cells and IL-10. Journal of Translational Medicine. 2016 Jun 16;14(1):1–11.
10. DiNardo AR, Rajapakshe K, Nishiguchi T, Grimm SL, Mtetwa G, Dlamini Q, et al. DNA hypermethylation during tuberculosis dampens host immune responsiveness. Journal of Clinical Investigation. 2020 Jun 1;130(6):3113–23.
11. Hong BY, Maulén NP, Adami AJ, Granados H, Balcells ME, Cervantes J. Microbiome changes during tuberculosis and antituberculous therapy. Clinical Microbiology Reviews. 2016 Oct 1;29(4):915–26.
12. Maloho RF, Putri Solikah M. Hubungan jamur Candida albicans dan Aspergillus fumigatus terhadap pasien tuberkulosis paru di balaI Laboratorium Kesehatan Daerah (BLKD) Provinsi Sulawesi Utara. Jurnal Analisis Laboratorium Medis. 2023 Dec 19;8(2):108–16.
13. Dewi I, Soeroto AY, Putriyani G, Hanifah W, Permata A, Annisa J, et al. Aspergillus fumigatus-specific antibodies in patients with chronic tuberculosis. International Journal Tuberculosis Lung Disease. 2020 Aug 1;24(8):853–6.
14. Chedid C, Kokhreidze E, Tukvadze N, Banu S, Uddin MKM, Biswas S, et al. Association of baseline white blood cell counts with tuberculosis treatment outcome: a prospective multicentered cohort study. International Journal of Infectious Disease. 2020 Nov 1;100:199–206.
15. Conti HR, Gaffen SL. IL-17–Mediated Immunity to the Opportunistic Fungal Pathogen Candida albicans . J Immunol. 2015 Aug 1;195(3):780–8.
16. Huppler AR, Conti HR, Hernández-Santos N, Darville T, Biswas PS, Gaffen SL. Role of Neutrophils in IL-17–Dependent Immunity to Mucosal Candidiasis. Journal of Immunology. 2014 Feb 15;192(4):1745–52.
17. Lopes JP, Lionakis MS. Pathogenesis and virulence of Candida albicans. Virulence. 2022;13(1):89–121.
18. Amiri MRJ, Siami R, Khaledi A. Tuberculosis Status and Coinfection of Pulmonary Fungal Infections in Patients Referred to Reference Laboratory of Health Centers Ghaemshahr City during 2007-2017. Ethiopian Journal of Health Sciences. 2018 Nov 1;28(6):683–90.
19. Hadadi‐Fishani M, Shakerimoghaddam A, Khaledi A. Candida coinfection among patients with pulmonary tuberculosis in Asia and Africa; A systematic review and meta-analysis of cross-sectional studies. Microbial Pathogenesis. 2020 Feb 1;139:1–7.
20. Orlandini RK, Rocha ACSD, Silva GA, Watanabe E, Motta ACF, Silva-Lovato CH, et al. Increased diversity, fungal burden, and virulence of oral Candida spp. in patients undergoing anti-tuberculosis treatment. Microbial Pathogenesis. 2021 Dec 1;161:1–12.
21. Utami F, Salam A, Handoko W. Hubungan usia, jenis kelamin-dan tingkat kepositifan dengan konversi basil tahan asam pasien tuberkulosis di unit pengobatan penyakit paru-paru Pontianak. 2014.
22. Fontalvo DM, Borre G, Camargo DG, Jimenez NC. Tuberculosis and fungal co-infection present in a previously healthy patient. Colombia Medica. 2016;47(2):105–8.
23. World Health Organization. Geneva : WHO Library Cataloguing-in-Publcation Data. 2022. p. 1–10 Global tuberculosis report 2022.
24. Baumgardner DJ. Oral Fungal Microbiota: To Thrush and Beyond. J Patient-Centered Res Rev. 2019 Oct 28;6(4):252–61.
25. Cao D, Liu W, Lyu N, Li B, Song W, Yang Y, et al. Gut Mycobiota Dysbiosis in Pulmonary Tuberculosis Patients Undergoing Anti-Tuberculosis Treatment. Microbiology Spectrum. 2021;9(3):1–13.
26. Alley TF, Moscatello K. Immunology and Microbiology. New York: Kaplan, Inc; 2016. p. 3–13.
27. Chimenz R, Tropeano A, Chirico V, Ceravolo G, Salpietro C, Cuppari C. IL-17 serum level in patients with chronic mucocutaneous candidiasis disease. Pediatric Allergy and Immunology. 2022 Jan 1;33(S27):77–9.
28. Whibley N, Tritto E, Traggiai E, Kolbinger F, Moulin P, Brees D, et al. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis. Journal of Leukocyte Biology. 2016 Jun 1;99(6):1153–64.
29. Aggor FEY, Break TJ, Trevejo-Nuñez G, Whibley N, Coleman BM, Bailey RD, et al. Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis. Science Immunology. 2020 Jun 5;5(48):1–30.
30. Zhou Y, Cheng L, Lei YL, Ren B, Zhou X. The Interactions Between Candida albicans and Mucosal Immunity. Frontiers in Microbiology. 2021 Jun 21;12:1–12.
31. Marits P, Wikström AC, Popadic D, Winqvist O, Thunberg S. Evaluation of T and B lymphocyte function in clinical practice using a flow cytometry based proliferation assay. Clinical Immunology. 2014;153(2):332–42.
32. Geissal ED, Coffey T, Gilbert DN. Clinical Importance of the Failure to Detect Immature Neutrophils by an Automated Hematology Analyser Background: Hospital clinical laboratories increasingly use automated. Infectious Diseases Clinical Practice [Internet]. 2010;18(6). Available from: www.infectdis.com
33. La Gioia A, Devito A, Fiorini F, Bombara M, Isola P, Spinale B, et al. Cytographic changes on BC-6800 Haematological Analyser related to the presence of Candida albicans in peripheral blood. A new tool to suspect candidemia? Journal of Clinical Pathology. 2017 Jun 1;70(6):494–9.
34. He Y, Liu J, Chen Y, Yan L, Wu J. Neutrophil Extracellular Traps in Candida albicans Infection. Front Immunol. 2022 Jun 16;13:1–7.
35. Stoimenou M, Tzoros G, Skendros P, Chrysanthopoulou A. Methods for the Assessment of NET Formation: From Neutrophil Biology to Translational Research. International Journal of Molecular Sciences. 2022 Dec 1;23(24):1–16.
36. Kılıçaslan Ayna T, Akman B, Özkızılcık Koçyiğit A, Güleç D, Tugmen C, Soyöz M. Flow cytometric evaluation of T and B lymphocyte percentage in chronic kidney disease. Medical Research Journal. 2017 Sep 21;2(1):29–33.
37. Rovati B, Mariucci S, Poma R, Tinelli C, Delfanti S, Pedrazzoli P. An eight-colour flow cytometric method for the detection of reference values of lymphocyte subsets in selected healthy donors. Clinical and Experimental Medicine. 2014;14(3):249–59.
38. Le Dang-Khoa Tan, Bui Avy An, Yu Zexi. An automated framework for counting lumpocytes from microscopic images. Vancouver: Institute of Electrical and Electronics Engineers; 2015. p. 421
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Vycke Yunivita, Mutiara Anastasia, Intan M.W Dewi, Chrysanti Murad
This work is licensed under a Creative Commons Attribution 4.0 International License.
